Mass kinetics of apolipoprotein A-I in interstitial fluid after administration of intravenous apolipoprotein A-I/lecithin discs in humans

Hovorka, Roman; Nanjee, M. Nazeem; Cooke, C. Justin; Miller, Irina P.; Olszewski, Waldemar L.; Miller, N. E.

doi:10.1194/jlr.m500358-jlr200

Cited by 12 publications

(8 citation statements)

References 26 publications

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“…The second pool is likely the interstitial pool of HDL, in which HDL has a mean residence time of approximately 29 hours (33). Thus, the second rise of apoA1 may mark the return of HDL to plasma after its transit through the interstitium, much of it likely in transit through the large organ of the skin.…”

Section: Resultsmentioning

confidence: 99%

“…Subsequent in vitro incubation studies showed that lipoprotein remodeling in interstitial fluid generates preβ-HDL from α-HDL, in contrast to plasma in which there is net conversion in the reverse direction (7). That the duration of these incubations was no greater than the apparent average residence time of HDL in the extracellular matrix in humans (33) suggests that this process may be an important source of preβ-HDLs in vivo.…”

Section: Figurementioning

confidence: 99%

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Lymphatic transport of high-density lipoproteins and chylomicrons

Randolph¹,

Miller²

2014

J. Clin. Invest.

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180

158

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The life cycles of VLDLs and most LDLs occur within plasma. By contrast, the role of HDLs in cholesterol transport from cells requires that they readily gain access to and function within interstitial fluid. Studies of lymph derived from skin, connective tissue, and adipose tissue have demonstrated that particles as large as HDLs require transport through lymphatics to return to the bloodstream during reverse cholesterol transport. Targeting HDL for therapeutic purposes will require understanding its biology in the extravascular compartment, within the interstitium and lymph, in health and disease, and we herein review the processes that mediate the transport of HDLs and chylomicrons through the lymphatic vasculature.

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Section: Resultsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Lymphatic transport of high-density lipoproteins and chylomicrons

Randolph¹,

Miller²

2014

J. Clin. Invest.

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180

158

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“…This might, to some part, relate to the decreased albumin concentration gradient between plasma and the extracellular space. Very little is known about the exact concentrations of extracellular albumin in surgical patients, but in volunteers levels of 5–25 g/L are reported in leg lymph by lymph vessel cannulation [ 29 ]. By micro dialysis tissue levels of 13.2 g/L are reported in skeletal muscle of volunteers [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Albumin Kinetics in Patients Undergoing Major Abdominal Surgery

et al. 2015

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BackgroundThe drop in plasma albumin concentration following surgical trauma is well known, but the temporal pattern of the detailed mechanisms behind are less well described. The aim of this explorative study was to assess changes in albumin synthesis and transcapillary escape rate (TER) following major surgical trauma, at the time of peak elevations in two well-recognized markers of inflammation.MethodsThis was a clinical trial of radiolabeled human serum albumin for the study of TER and plasma volume. Ten patients were studied immediately preoperatively and on the 2nd postoperative day after major pancreatic surgery. Albumin synthesis rate was measured by the flooding dose technique employing incorporation of isotopically labelled phenylalanine.ResultsFractional synthesis rate of albumin increased from 11.7 (95% CI: 8.9, 14.5) to 15.0 (11.7, 18.4) %/day (p = 0.027), whereas the corresponding absolute synthesis rate was unchanged, 175 (138, 212) versus 150 (107, 192) mg/kg/day (p = 0.21). TER was unchanged, 4.9 (3.1, 6.8) %/hour versus 5.5 (3.9, 7.2) (p = 0.63). Plasma volume was unchanged but plasma albumin decreased from 33.5 (30.9, 36.2) to 22.1 (19.8, 24.3) g/L. (p<0.001).ConclusionTwo days after major abdominal surgery, at the time-point when two biomarkers of generalised inflammation were at their peak and the plasma albumin concentration had decreased by 33%, we were unable to show any difference in the absolute synthesis rate of albumin, TER and plasma volume as compared with values obtained immediately pre-operatively. This suggests that capillary leakage, if elevated postoperatively, had ceased at that time-point. The temporal relations between albumin kinetics, capillary leakage and generalised inflammation need to be further explored.Trial Registrationclinicaltrialsregister.eu: EudraCT 2010-08529-21 ClinicalTrials.gov NCT01194492

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“…With this data, the authors estimated a whole-body reverse cholesterol transport rate of 344 mg/day via the lymph. Therefore, given that lymph flow, and consequently lipoprotein transport, varies in lymphatics with posture and activity level [48], it is important to consider lymphatic transport when modeling lipoprotein kinetics [49]. This is especially important in pathologies where lymphatic function is compromised.…”

Section: Lymphatic Role In Reverse Cholesterol Transportmentioning

confidence: 99%

Lymphatic lipid transport: sewer or subway?

Dixon

2010

Trends in Endocrinology & Metabolism

143

132

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The lymphatics began receiving attention in the scientific community as early as 1622, when Gasparo Aselli noted the appearance of milky white vessels in the mesentery of a well-fed dog. Since this time, the lymphatic system has been historically regarded as the sewer of the vasculature, passively draining fluid and proteins from the interstitial spaces (along with lipid from the gut) into the blood. Recent reports, however, suggest that the lymphatic role in lipid transport is an active and intricate process and when lymphatic function is compromised, there are systemic consequences to lipid metabolism and transport. This review highlights these recent findings and suggests future directions for understanding the interplay between lymphatic and lipid biology in health and disease. Lymphatic FunctionThe lymphatic system (Figure 1) is found in most tissues in the body and plays important roles in maintaining fluid balance [1], immune cell trafficking from the periphery to lymph nodes [2], and lipid transport from the intestine to the circulation [3]. The lymphatic vasculature is comprised of unique functional features that enable entry and transport of large proteins, immune cells, lipids, and fluid against a pressure gradient (Figure 2). Specifically, the entry point of the lymphatic system is regulated by initial lymphatics (blind ended microvessels lacking smooth muscle), which have specialized junctions that prevent backflow of fluid into the tissue after it has entered the vessel [4,5]. The initial lymphatics merge into larger collecting vessels composed of individually contracting units known as lymphangions. Each lymphangion is lined with a functionally unique form of smooth muscle that provides vessel tone and allows the vessel to contract down to as much as 20% of its resting diameter [6,7]. These contractions, when combined with the valve leaflets that separate each lymphangion [8], promote unidirectional propagation of flow [9]. In this review we specifically focus on the lymphatic vasculature's role in lipid metabolism and trafficking, highlighting recent work that suggests a connection between lymphatic dysfunction and lipid-related diseases such as obesity and hyperlipidemia.

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Mass kinetics of apolipoprotein A-I in interstitial fluid after administration of intravenous apolipoprotein A-I/lecithin discs in humans

Cited by 12 publications

References 26 publications

Lymphatic transport of high-density lipoproteins and chylomicrons

Lymphatic transport of high-density lipoproteins and chylomicrons

Albumin Kinetics in Patients Undergoing Major Abdominal Surgery

Lymphatic lipid transport: sewer or subway?

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